Reward dysfunction in AD/HD

BACKGROUND: Research has started conceptualizing sluggish cognitive tempo (SCT) within the Research Domain Criteria (RDoC), but no study has tested SCT symptomatology in relation to the positive valence systems. METHODS: Participants (N = 4,679; 18-29 years; M = 19.08, SD = 1.36; 69% female; 80.9% White) enrolled in six universities in the United States completed self-reported measures of positive valence systems, SCT, and psychopathology dimensions. RESULTS: SCT symptoms were uniquely associated with greater reward valuation and expectancy of reward, but less willingness to work for reward...

The transcription factor NURR1 regulates the dopamine (DA) signaling pathway and exerts a critical role in the development of midbrain dopaminergic neurons (mDA). NURR1 alterations have been linked to DA-associated brain disorders, such as Parkinson's disease and schizophrenia. However, the association between NURR1 defects and the attention-deficit hyperactivity disorder (ADHD), a DA-associated brain disease characterized by hyperactivity, impulsivity and inattention, has never been demonstrated. To date, a comprehensive murine model of ADHD truly reflecting the whole complex human psychiatric disorder still does not exist...

The major ascending neuromodulator dopamine has long been implicated in cognitive control. Effects of dopamine-related disorders and the treatment of the cognitive control deficits associated with these disorders are commonly attributed to modulation of the prefrontal cortex. However, many disorders that are accompanied by cognitive control deficits also implicate abnormal dopamine transmission in the striatum, which has been associated more readily with value-based learning, choice, and motivation. We put forward the hypothesis that effects of dopamine on cognitive control reflect, in part, indirect modulation of value-based learning and choice computations that alter the motivation to exert control...

BACKGROUND: A recent neurocognitive model of attention-deficit hyperactivity disorder (ADHD) has proposed a primary deficit in reward function as well as in executive function to account for underlying neural substrates of ADHD symptoms. Atomoxetine has been widely used as a non-stimulant medication for ADHD with little abuse liability. Although animal studies have reported that atomoxetine increases extracellular levels of both noradrenaline and dopamine in the prefrontal cortex, which receives input from a mesocorticolimbic pathway involved in reward function, there have been few studies in humans concerning the effects of atomoxetine in terms of reward function...

BACKGROUND: A reduced willingness to perform effort based on the magnitude and probability of potential rewards has been associated with diminished dopamine function and may be relevant to attention-deficit/hyperactivity disorder (ADHD). Here, we investigated the influence of ADHD status and methylphenidate on effort-based decisions. We hypothesized that ADHD participants would make fewer high-effort selections than non-ADHD subjects, and that methylphenidate would increase the number of high-effort selections...

The dopamine projection from ventral tegmental area (VTA) to nucleus accumbens (NAc) is critical for motivation to work for rewards and reward-driven learning. How dopamine supports both functions is unclear. Dopamine cell spiking can encode prediction errors, which are vital learning signals in computational theories of adaptive behaviour. By contrast, dopamine release ramps up as animals approach rewards, mirroring reward expectation. This mismatch might reflect differences in behavioural tasks, slower changes in dopamine cell spiking or spike-independent modulation of dopamine release...

RATIONALE: Males are more prone to psychosis, schizophrenia and substance abuse and addiction in adolescence and early adulthood than females. However, the role of androgens during this developmental period is poorly understood. OBJECTIVES: This study aimed to examine how androgens in adolescence influence psychosis-like behaviour in adulthood and whether brain-derived neurotrophic factor (BDNF) is a mediator of these developmental effects. METHODS: Wild-type and BDNF heterozygous male mice were castrated at pre-pubescence and implanted with testosterone or dihydrotestosterone (DHT)...

Deficits in motivation are at the core of many neuropsychiatric disorders, including major depressive disorder (MDD). Research in MDD has been heavily focused on anhedonia and depression or negative/positive symptoms of depression, with less research attention focused on the dysregulation of motivational processes. Opioid receptors are widely distributed throughout the brain, particularly in areas implicated in motivation, especially the striatum, nucleus accumbens, medial prefrontal cortex, hippocampus, ventral tegmental area, hypothalamus, and amygdala...

Cognitive control is necessary for goal-directed behavior, yet people treat cognitive control demand as a cost, which discounts the value of rewards in a similar manner as other costs, such as delay or risk. It is unclear, however, whether the subjective value (SV) of cognitive effort is encoded in the same putatively domain-general brain valuation network implicated in other cost domains, or instead engages a distinct frontoparietal network, as implied by recent studies. Here, we provide rigorous evidence that the valuation network, with core foci in the ventromedial prefrontal cortex and ventral striatum, also encodes SV during cognitive effort-based decision-making in healthy, male and female adult humans...

Choice impulsivity is an important subcomponent of the broader construct of impulsivity and is a key feature of many psychiatric disorders. Choice impulsivity is typically quantified as temporal discounting, a well-documented phenomenon in which a reward's subjective value diminishes as the delay to its delivery is increased. However, an individual's proclivity to-or more commonly aversion to- risk can influence nearly all of the standard experimental tools available for measuring temporal discounting. Despite this interaction, risk preference is a behaviourally and neurobiologically distinct construct that relates to the economic notion of utility or subjective value...

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental disorder, putatively induced by dissociable dysfunctional biobehavioral pathways. Here, we present a proof-of-concept study to parse ADHD-related heterogeneity in its underlying neurobiology by investigating functional connectivity across multiple brain networks to 1) disentangle categorical diagnosis-related effects from dimensional behavior-related effects and 2) functionally map these neural correlates to neurocognitive measures...

Importance: Anhedonia can present in children and predict detrimental clinical outcomes. Objective: To map anhedonia in children onto changes in intrinsic large-scale connectivity and task-evoked activation and to probe the specificity of these changes in anhedonia against other clinical phenotypes (low mood, anxiety, and attention-deficit/hyperactivity disorder [ADHD]). Design, Setting, and Participants: Functional magnetic resonance imaging (fMRI) data were from the first annual release of the Adolescent Brain Cognitive Development study, collected between September 2016 and September 2017 and analyzed between April and September 2018...

OBJECTIVE: The present study aimed to detect differences in the reward response between adults with attention deficit hyperactivity disorder (ADHD) and healthy controls (HCs) using functional magnetic resonance imaging (fMRI). METHODS: The Iowa gambling task (IGT) was designed to explore participants' reward-related decision-making in relation to selections during risky behaviors. Twenty adults with ADHD and 20 HCs were enrolled. fMRI with a modified IGT was performed...

Delayed reward discounting (DRD) is a behavioral economic measure of impulsivity, reflecting how rapidly a reward loses value based on its temporal distance. In humans, more impulsive DRD is associated with susceptibility to a number of psychiatric diseases (e.g., addiction, ADHD), health outcomes (e.g., obesity), and lifetime outcomes (e.g., educational attainment). Although the determinants of DRD are both genetic and environmental, this review focuses on its genetic basis. Both rodent studies using inbred strains and human twin studies indicate that DRD is moderately heritable, a conclusion that was further supported by a recent human genome-wide association study (GWAS) that used single nucleotide polymorphisms (SNP) to estimate heritability...

OBJECTIVE: Risk-taking during adolescence is a leading cause of mortality; Neuroscience research examining pubertal effects on decision-making is needed to better inform interventions, particularly among youth with attention-deficit/hyperactivity (ADHD) and disruptive behavior disorders (DBD), who are particularly prone to risky decision-making. We examined effects of pubertal development on risky decision-making and neural activation during decision-making among youth with ADHD/DBDs...

BACKGROUND: Activation of brain insulin receptors modulates reward sensitivity, inhibitory control and memory. Variations in the functioning of this mechanism likely associate with individual differences in the risk for related mental disorders (attention deficit hyperactivity disorder or ADHD, addiction, dementia), in agreement with the high co-morbidity between insulin resistance and psychopathology. These neurobiological mechanisms can be explored using genetic studies. We propose a novel, biologically informed genetic score reflecting the mesocorticolimbic and hippocampal insulin receptor-related gene networks, and investigate if it predicts endophenotypes (impulsivity, cognitive ability) in community samples of children, and psychopathology (addiction, dementia) in adults...

Impatience-the failure to wait or tolerate delayed rewards (e.g. food, drug and monetary incentives)-is a common behavioural tendency in humans. However, when rigidly and rapidly expressed with limited regard for future, often negative consequences, impatient or impulsive actions underlie and confer susceptibility for such diverse brain disorders as drug addiction, attention-deficit hyperactivity disorder (ADHD) and major depressive disorder. Consequently, 'waiting' impulsivity has emerged as a candidate endophenotype to inform translational research on underlying neurobiological mechanisms and biomarker discovery for many of the so-called impulse-control disorders...

Despite many studies examining a combination of self-report, behavioral, and neurophysiological measures, only few address whether these different levels of measurement indeed reflect one construct. The present study aids in filling this gap by exploring the association between self-report, behavioral, and electrophysiological measures of impulsivity and related constructs such as sensation seeking, reward responsiveness, and ADHD symptoms. Individuals across two large samples (n = 133 and n = 142) completed questionnaires and performed behavioral tasks (the Eriksen Flanker task, the Go/No-Go task, the Reward task, and the Balloon Analogue Risk Task) during which brain activity was measured using electroencephalography (EEG)...

OBJECTIVE: Models of ADHD consider the influence of situational factors on cognitive performance and symptoms. METHOD: The influence of acute physical exercise, stimulation through continuous fine motor movement, and performance-related reward on performance and ADHD symptoms was assessed. Thirty-six adults with ADHD and 36 healthy controls performed executive function tasks (EF-tasks) of inhibition, selective attention, and working memory with material close to daily life...

In children with Tourette syndrome (TS), tics are often attributed to deficient self-control by health-care professionals, parents, and peers. In this behavioural study, we examined response inhibition in TS using a modified Simon task which probes the ability to solve the response conflict between a new non-spatial rule and a highly-overlearned spatial stimulus-response mapping rule. We applied a distributional analysis to the behavioural data, which grouped the trials according to the individual distribution of reaction times in four time bins...